Here is the abstract from next Friday's presentation. It will be interesting to see if the immune response seen in the HS-410 combination cohort results in enhanced 2 year RFS results. BCG alone does not produce this immunologic response and recurrence can occur in as many as 40% of patients between year 1 and 2. We should get fuller topline results next September or October IMO.
Immune response results of vesigenurtacel-l (HS-410) in combination with BCG from a randomized phase II trial in patients with non-muscle invasive bladder cancer (NMIBC).
Sub-category:
Urothelial Carcinoma
Category:
Genitourinary Cancer
Meeting:
2017 Genitourinary Cancers Symposium
Abstract No:
319
Poster Board Number:
Poster Session B (Board #F8)
Citation:
J Clin Oncol 35, 2017 (suppl 6S; abstract 319)
Author(s): Gary D. Steinberg, Neal D. Shore, Lawrence Ivan Karsh, James L. Bailen, Trinity J. Bivalacqua, Karim Chamie, James S. Cochran, Richard David, Robert L. Grubb, Wael A. Harb, Jeffrey M. Holzbeierlein, Ashish M. Kamat, Edouard John Trabulsi, William Vincent Walsh, Michael Brandon Williams, Fredrick Wolk, Michael Woods, Melissa Leigh Price, Brandon Early, Taylor Houghton Schreiber; Section of Urology, Department of Surgery, University of Chicago Pritzker School of Medicine, Chicago, IL; Carolina Urologic Research Center, Myrtle Beach, SC; The Urology Center of Colorado, Denver, CO; First Urology Research, Louisville, KY; The James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, MD; University of California, Los Angeles, Los Angeles, CA; Urology Clinics of North Texas, Dallas, TX; Skyline Urology, Sherman Oaks, CA; Washington University School of Medicine in St. Louis, St. Louis, MO; Horizon Oncology Center, Lafayette, IN; The University of Kansas Hospital, Kansas City, KS; The University of Texas MD Anderson Cancer Center, Houston, TX; The Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA; University of Massachusetts Medical School, Worcester, MA; Md Anderson Cancer Ctr, Virginia Beach, VA; Skyline Urology, Torrance, CA; The University of North Carolina at Chapel Hill, Chapel Hill, NC; Heat Biologics, Durham, NC
Abstract Disclosures
Abstract:
Background: Vesigenurtacel-L (HS-410) is a vaccine comprised of an allogeneic cell line, selected for high expression from a series of bladder tumor antigens, and transfected with gp96-Ig. Cell-secreted gp96-Ig delivers these cell-derived antigens to a recipient's own antigen presenting cells, activating CD8+ cytotoxic T cells. Here we present the secondary immune outcomes from a randomized Phase 2 trial with HS-410 in combination with BCG in NMIBC. Trial ID NCT02010203. Methods: 78 patients with intermediate- (n=5) or high-risk (n=73) NMIBC who are either BCG-naïve or recurrent, with or without carcinoma in situ (CIS), were enrolled 1:1:1 to one of two doses of HS-410 (either 106 or 107cells/dose) or placebo in combination with 6 weeks of induction BCG, followed by 6 more weeks of HS-410 in the induction phase. Maintenance treatment consisted of 3-weekly treatments at the following timepoints: 3 mo., 6 mo., 12 mo. Concurrently, 16 patients (1 int. risk, 15 high-risk) were enrolled in an open-label monotherapy HS-410 arm for patients who did not receive BCG. The primary endpoint was 1-year RFS. Secondary immune evaluations include ELISPOT, tumor IHC, tumor antigen profiling, flow cytometry, urine cytokine analysis, and T cell receptor sequencing. Results: HS-410 treatment was well tolerated; AE profiles were similar across the treatment arms. HS-410 antigen expression showed prominent overlap with patient tumors. IFN? ELISPOT assay demonstrated a high baseline response to HS-410; responses to overlapping peptide pools of HS-410 derived antigens defined immune responders (doubling of IFN?-secreting cells). IHC demonstrated that ~60% of NMIBC patient tumor biopsies were TIL negative at baseline (n=84), but that only ~15% of tumor biopsies were TIL negative post treatment (n=40). Thus, TIL status may be further used to define a responder and non-responder population to HS-410. Conclusions: Vesigenurtacel-L is well-tolerated, and immunologic responses consistent with vaccine mechanism of action may correlate with efficacy and suggest future biomarkers. Vesigenurtacel-L warrants further investigation as a potential treatment for NMIBC. Clinical trial information: NCT02010203
